Impact of COVID‐19 lockdown restrictions on hepatitis C testing in Australian primary care services providing care for people who inject drugs

Abstract In 2020, the Australian state of Victoria experienced the longest COVID‐19 lockdowns of any jurisdiction, with two lockdowns starting in March and July, respectively. Lockdowns may impact progress towards eliminating hepatitis C through reductions in hepatitis C testing. To examine the impact of lockdowns on hepatitis C testing in Victoria, de‐identified data were extracted from a network of 11 services that specialize in the care of people who inject drugs (PWID). Interrupted time‐series analyses estimated weekly changes in hepatitis C antibody and RNA testing from 1 January 2019 to 14 May 2021 and described temporal changes in testing associated with lockdowns. Interruptions were defined at the weeks corresponding to the start of the first lockdown (week 14) and the start (week 80) and end (week 95) of the second lockdown. Pre‐COVID, an average of 80.6 antibody and 25.7 RNA tests were performed each week. Following the first lockdown in Victoria, there was an immediate drop of 23.2 antibody tests and 8.6 RNA tests per week (equivalent to a 31% and 46% drop, respectively). Following the second lockdown, there was an immediate drop of 17.2 antibody tests and 4.6 RNA tests per week (equivalent to a 26% and 33% drop, respectively). With testing and case finding identified as a key challenge to Australia achieving hepatitis C elimination targets, the cumulative number of testing opportunities missed during lockdowns may prolong efforts to find, diagnose and engage or reengage in care of the remaining population of PWID living with hepatitis C.


| INTRODUC TI ON
A key pillar of public health responses to COVID-19 has been various levels and periods of 'lockdown', which have included restrictions on people's movements and the closing of workplaces, services and social venues. While health services have general remained open during these periods, health system pressures associated with COVID-19 1 and community concerns about attending health services and COVID-19 acquisition risk [2][3][4] have challenged the maintenance of routine health service delivery. Of great concern is the impact of the pandemic and subsequent government-imposed restrictions on access to healthcare, 5,6 including testing and treatment for other communicable diseases. Global disease elimination strategies, which necessitate high rates of testing and treatment among priority populations such as those for the elimination of hepatitis B and hepatitis C, are likely to be hindered by widespread reductions in access to healthcare during the COVID-19 pandemic.
Australia has a longstanding strategic response to hepatitis C and has set national targets that align with global elimination targets set by the WHO that aim to reduce hepatitis C incidence by 90% compared with 2015 levels by 2030. 7 High coverage of testing among people who inject drugs (PWID) and access to treatment for all are key to Australia's hepatitis C elimination strategy. 8 While the availability of direct-acting antiviral (DAA) therapy in 2016 leads to a rapid escalation in testing and case finding, decelerating rates of testing and case-finding since late 2016 are threatening Australia's HCV elimination progress. 9 Modelling work shows that without significant and sustained increases in testing among people exposed to HCV, including PWID and other people living with HCV, and subsequent timely referral to care and treatment, Australia will not reach its 2030 elimination goals. 10 Restrictions implemented in response to COVID-19 may further impact Australia's progress towards eliminating hepatitis C through reductions in hepatitis C testing. to retrospectively examine the impact of the preceding lockdowns during 2020 in Victoria on hepatitis C testing, as well as rates of recovery following these lockdowns, among individuals attending a network of services in Victoria specializing in the care of PWID.

| Data source
Clinical data were extracted from a network of 11 general practice and community health clinics in the state of Victoria participating in the Australian Collaboration for Coordinated Enhanced Sentinel

Surveillance of Blood Borne Viruses and Sexually Transmissible
Infections or ACCESS. 15 The ACCESS protocol has been published elsewhere. 15 ACCESS clinics included in this analysis were sentinel surveillance sites that were selected based on high hepatitis C caseloads and provision of services tailored towards PWID, including opioid agonist therapy prescribing and co-location with needle and syringe programs. Nine clinics were located in the Melbourne of the first lockdown (week 14) and the start (week 80) and end (week 95) of the second lockdown. Pre-COVID, an average of 80.6 antibody and 25.7 RNA tests were performed each week. Following the first lockdown in Victoria, there was an immediate drop of 23.2 antibody tests and 8.6 RNA tests per week (equivalent to a 31% and 46% drop, respectively). Following the second lockdown, there was an immediate drop of 17.2 antibody tests and 4.6 RNA tests per week (equivalent to a 26% and 33% drop, respectively). With testing and case finding identified as a key challenge to Australia achieving hepatitis C elimination targets, the cumulative number of testing opportunities missed during lockdowns may prolong efforts to find, diagnose and engage or reengage in care of the remaining population of PWID living with hepatitis C.

K E Y W O R D S
COVID-19, hepatitis C, lockdowns, people who inject drugs metropolitan area and two were in regional Victoria. Patient demographics and hepatitis C antibody and RNA test results were retrospectively extracted using GRHANITE™ data extraction software, which was designed specifically for the secure collection of deidentified health data. 16 Using GRHANITE, patient records are linked within and across sites using a highly sensitive algorithm which utilizes non-identifying probabilistic linkage keys derived from, but not containing, patient identifiers, including patient name, date of birth, sex and Medicare card number. 17

| Outcomes
Using data from all services during the 125 weeks between 1 January

| Observation periods
The unit of observation for this time-series analysis was weekly number of each outcome (tests/consultations) conducted across the network. Week number was defined as each consecutive 7-day pe- Using interrupted time-series analysis, it is recommended to have at least eight time points before and after the interruption in order to have sufficient power to estimate regression coefficients. 21 Additionally, at least eight time points are required between multiple interruption points in order to estimate their impact independently. 21 Given the short time between the end of the first lockdown and the start of the second lockdown, we were not able to assess an additional interruption at the end of the first lockdown. As such, the first lockdown period and the period between the end of the first lockdown and start of the second lockdown were considered as a single 14-week period. The third lockdown in Victoria was a 'snaplockdown' which lasted only 5 days and as such was not consider as a separate period. See Table S1 for timeline of lockdown restrictions and analysis observation periods.
For each outcome (antibody test, RNA test and consultation), over the entire study period and across each of the four defined observation periods, we calculated: (1) the total number of unique individual with the outcome (i.e. the number tested or the number with a consultation, respectively), (2) the total count of the outcome and (3) the average count of the outcome per week. We calculated the relative reduction in the average number of tests (for each of the testing outcomes) or consultations conducted per week during periods two, three and four compared with during period one (pre-COVID).

| Interrupted time-series analysis
To estimate trends in HCV testing and the number of consultations across each period, and to explore changes in testing and consultations at the introduction of lockdowns and the easing of the second lockdown, we performed three interrupted time-series analyses. Analyses were conducted by fitting Prais-Winston linear regression models, which account for autocorrelation between weekly observations. Three interruptions were chosen to reflect the beginning of each observation period. For each outcome, coefficients estimated from the interrupted time-series analysis included the prelockdown trend (β1, the estimated weekly mean change in outcome during period 1), the immediate change in outcome level at the start of each period (β2, β4, β6) and the change in slope at the beginning of each period (β3, β5, β7) (Box 1). We also calculated the trend during periods 2-4 with corresponding 95% confidence intervals and p-values. We report the predicted values at each interruption estimated using the trend prior to and after the interruption, respectively, and the relative differences. Analyses were disaggregated by sex. Vincent's Hospital (08/051). As our study analyses de-identified data collected under the auspices of public health surveillance, individual patient consent was not required. Individuals were able to opt-out of the surveillance system if they wish. Table 1 shows the average number of antibody tests, RNA tests, first-time HCV testers and consultations per week in period 1 (prelockdown), period 2 (during the first lockdown and prior to the second lockdown), period 3 (during the second lockdown) and period 4 (post-second lockdown).

| Antibody tests
A total of 8748 hepatitis C antibody tests were performed among 7812 individuals during the entire observation period. The mean number of antibody tests performed per week during period 1 was 80.6, which dropped to 58.4 during period 2 (28% less than pre-lockdown) and to 51.1 during period 3 (37% less than pre-lockdown). During the period 4, the weekly mean was 62.6 or 22% less than pre-lockdown. During period 3, the weekly mean was 11.7 (54% less compared with pre-lockdown). During period 4, the weekly mean was 12.8 or 50% less than pre-lockdown.

| First-time HCV testers
During the entire observation period, 5817 individuals were tested for HCV (antibody or RNA) for the first time recorded in the ACCESS system. The mean number of first-time HCV testers per week during period 1 was 54.9, which dropped to 38.3 during period 2 (30% less than pre-lockdown). During period 3, the weekly mean was 32.9 (40% less compared with pre-lockdown) and during period 4, the weekly mean was 39.5 (28 less than pre-lockdown).

| Consultations
During the entire observation period, there were a total of 685,004 clinical consultations among 103,341 individuals. The mean number of consultations occurring per week during period 1 was 5244.7, which increased to 5611.3 in period 2 (7% more than pre-lockdown) and to 5604.3 during period 3 (7% more than pre-lockdown). During period 4, the weekly mean number of consultations was 5862.3 or 12% more than the pre-lockdown period.  Table 2 shows regression coefficients for each interrupted timeseries model. Table 3 shows relative drops in testing and consultations associated with the introduction of each lockdown.  Figure 1A).

| Antibody tests
The declining trend in antibody testing pre-COVID was more pronounced among males; however, similar relative drops at the introduction of lockdowns were observed for males and females (Table S2).

| First-time HCV testers
The May 2021 ( Figure 1C). Similar to antibody testing, the declining trend in antibody testing pre-COVID was more pronounced among males; however, similar relative drops at the introduction of lockdowns were observed for males and females (Table S6).

| DISCUSS ION
Across this network of sentinel clinics specializing in the care of PWID, moderate drops in hepatitis C antibody and RNA testing TA B L E 3 Predicted values and relative level change at each interruption which is now well below an estimated minimum of 13,680 annual treatments needed to achieve elimination targets. 27  and healthcare providers, contributing to the observed drop in hepatitis C testing. Of note, the drop in first-time HCV testers at the start of the second lockdown (37%) was greater than the drop in antibody testing (26%) and RNA testing (33%) at the same time, highlighting the potential impact of the restrictions on engaging new patients in HCV testing. Efforts to both engage and re-engage clients in hepatitis C testing post-COVID will be crucial.
Ongoing transmission of COVID-19 globally suggests that COVID-19-related disruptions in Australia will likely continue to have a significant impact on the provision of healthcare for years to come.
While balancing COVID-19 response efforts with other healthrelated priorities such as hepatitis C elimination may be difficult, maintaining efforts towards elimination targets will be beneficial in the long term. The longer countries take to reach elimination, the less cost-effective elimination strategies become. 33 Keeping governments and clinicians engaged in hepatitis C elimination during and post-COVID will be essential in reaching 2030 elimination targets.
The full impact of COVID-19 lockdowns on HCV transmission within the community is not yet known. While notification data show declines in hepatitis C diagnoses during the COVID-19 era, 34 notification trends are likely influenced by drops in testing. Sentinel surveillance data, such as that collected by ACCESS, will play an important role in monitoring and estimating the effect of COVID-19 on hepatitis C incidence and in guiding strategies to promote a return to service engagement.
There are several limitations to our study. First, given that these data are de-identified prior to extraction from routine clinical and laboratory records, we were not able to disaggregate PWID explicitly from other individuals in the data set. Second, given the low number of weeks (time points) between the introduction of the first and second lockdown periods (period 2), we may not have been able to detect trends which did not reach statistical significance. Third, as we were unable to disaggregate telehealth consultations and face-to-face consultations, or disaggregate clinical consultations related to HCV care from general health consultations, we could not explore the impact of COVID-19 on HCV-related consultations directly.
Across this network of primary care clinics in Victoria, the implementation of state-wide lockdowns in response to COVID-19 during 2020 was associated with modest reductions in hepatitis C antibody and RNA testing. While some recovery in hepatitis C testing rates was observed in 2021, the cumulative number of testing opportunities missed during lockdowns may prolong efforts to find and diagnose the remaining population of PWID living with undiagnosed hepatitis C.